Carcinoma of the breast is the most common malignancy among women in North America, with 130,000 new cases in 1987. Approximately one in 11 women develop breast cancer in their lifetimes, causing this malignancy to be the second leading cause of cancer death among women in the United States, after lung cancer. Although the majority of women with breast cancer present with completely resectable disease, metastatic disease remains a formidable obstacle to cure. The use of adjuvant chemotherapy or hormonal therapy has definite positive impact on disease-free survival and overall survival in selected subsets of women with completely resected primary breast cancer, but a substantial proportion of women still relapse with metastatic disease (see, e.g., Fisher et al. (1986) J. Clin. Oncol. 4:929-941; "The Scottish trial", Lancet (1987) 2:171-175). In spite of the regularly induced objective responses induced by chemotherapy and hormonal therapy in appropriately selected patients, cure of metastatic breast cancer has not been achieved (see e.g., Aisner, et al. (187) J. Clin. Oncol. 5:1523-1533). To this end, many innovative treatment programs including the use of new agents, combinations of agents, high dose therapy (Henderson, ibid.) and increased dose intensity (Kernan et al. (1988) Clin. Invest. 259:3154-3157) have been assembled. Although improvements have been observed, routine achievement of complete remissions of metastatic disease, the first step toward cure, has not occurred. There remains a pressing need for new approaches to treatment.
The Fv fragment of an immunoglobulin molecule from IgM, and on rare occasions IgG or IgA, is produced by proteolytic cleavage and includes a non-covalent V.sub.H -V.sub.L heterodimer representing an intact antigen binding site. A single chain Fv (sFv) polypeptide is a covalently linked V.sub.H -V.sub.L heterodimer which is expressed from a gene fusion including V.sub.H - and V.sub.L -encoding genes connected by a peptide-encoding linker. See Huston et al., 1988, Proc. Nat. Aca. Sci. 85: 5879, hereby incorporated by reference.
U.S. Pat. No. 4,753,894 discloses murine monoclonal antibodies which bind selectively to human breast cancer cells and, when conjugated to ricin A chain, exhibit a TCID 50% against at least one of MCF-7, CAMA-1, SKBR-3, or BT-20 cells of less than about 10 nM. The SKBR-3 cell line is recognized specifically by the monoclonal antibody 520C9. The antibody designated 520C9 is secreted by a murine hybridoma and is now known to recognize c-erbB-2 (Ring et al., 1991, Molecular Immunology 28:915).